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Objective This study aimed to explore the effect of bronchopulmonary dysplasia (BPD) on the early intellectual development of preterm infants. Methods From 2011 to 2015, 83 preterm infants diagnosed with BPD were recruited to the BPD group, and 89 preterm infants without BPD and 98 healthy term infants were randomly recruited to the non-BPD and term group, respectively. Neural and intellectual development according to the Gesell Development Scale were evaluated and compared between groups at 0-3 months, 3-6 months, 6-9 months, and 9-12 months of adjusted age for preterm infants and real age for term infants. Multivariate logistic regression was used to determine the associations between BPD and adverse neurological outcomes at 9-12 months of adjusted age. Results Compared to term infants, preterm infants had significantly lower developmental quotients for adaptability, gross motor, fine motor, language and social intercourse skills. At follow-up, deficits in one or more neurofunctions related to adaptability, gross motor, fine motor, language and social intercourse skills were significantly more frequent in preterm children with BPD than in those with no history of BPD. BPD was independently associated with adverse neurological outcomes at 9-12 months of adjusted age in preterm infants. Conclusions Early intelligence disturbances occurred significantly more frequently in BPD infants than non-BPD infants. Monitoring of the development of the nervous system in BPD infants should be strengthened. This article is protected by copyright. All rights reserved.

// Shih-Wen Chen 1, * , Chiang-Ting Chou 2, 3, * , Cheng-Chi Chang 1, 4, 5, 6, 7, 8 , Yue-Ju Li 4 , Szu-Ta Chen 9, 10 , I-Ching Lin 11, 12, 13 , Sang-Heng Kok 14, 15 , Shih-Jung Cheng 1, 4, 15 , Jang-Jaer Lee 7 , Tai-Sheng Wu 4 , Min-Liang Kuo 17 , Been-Ren Lin 16 1 Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan 2 Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi, Taiwan 3 Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi, Taiwan 4 Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan 5 Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan 6 Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan 7 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 8 Department of Biotechnology, Asia University, Taichung, Taiwan 9 Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan 10 Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 11 School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 12 Department of Family Medicine, Changhua Christian Hospital, Changhua, Taiwan 13 School of Medicine, Chung Shan Medical University, Taichung, Taiwan 14 Division of Oral and Maxillofacial Surgery, Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan 15 Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan 16 Department of Surgery, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan 17 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan * These authors contributed equally to this work Correspondence to: Been-Ren Lin, email: beenrenlin@ntu.edu.tw Keywords: HMGCS2, PPARα, metastasis, CRC, OSCC Received: May 31, 2016 Accepted: October 21, 2016 Published: November 01, 2016 ABSTRACT Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro , ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer.

Background Glycolysis machinery regulates cancer cell behavior. However, the roles of these glycolysis enzymes in oral squamous cell carcinoma (OSCC) progression remain unknown. Methods Fructose-bisphosphate aldolase C (ALDOC) expression in OSCC patients and cell lines was detected using quantitative real-time polymerase chain reaction (PCR). The functions of ALDOC in migration and invasion were determined using gain and loss of function approaches. An orthotopic OSCC animal model was performed to investigate the effects of ALDOC on metastasis and tumorigenesis in vivo. Results ALDOC expression is negatively significantly correlated with clinical outcome and cell migration in vitro and in vivo. ALDOC blocks adenosine triphosphate generation and lactate production, and mutation constructs of Arg42 and Lys146 functionally restore ALDOC-inhibited cell migration and invasion. Conclusion ALDOC functions as an OSCC prognosis marker clinically, and suppresses migration and invasion by its catalytic domain of Arg42 and Lys146. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

The aim of this study is to introduce a self-designed, minimally invasive technique for repairing an acute Achilles tendon rupture percutaneously. Comparing with the traditional open repair, the new technique provides obvious advantages of minimized operation-related lesions, fewer wound complications as well as a higher healing rate. However, a percutaneous technique without direct vision may be criticized by its insufficient anastomosis of Achilles tendon and may also lead to the lengthening of the Achilles tendon and a reduction in the strength of the gastrocnemius. To address the potential problems, we have improved our technique using a percutaneous Kirschner wire leverage process before suturing, which can effectively recover the length of the Achilles tendon and ensure the broken ends are in tight contact. With this improvement in technique, we have great confidence that it will become the treatment of choice for acute Achilles tendon ruptures.

ObjectiveThe aim of this study was to investigate the therapeutic response and toxicity of intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (c-RT) as adjuvant therapy in patients with pelvic locoregional recurrence of cervical cancer after radical surgery.MethodsThis retrospective study included 161 patients with unresectable pelvic locoregional recurrence of cervical cancer after radical surgery between March 2003 and May 2012. All patients were initially diagnosed with International Federation of Gynecology and Obstetrics stage IB-IIA cervical cancer and received radical hysterectomy and pelvic lymphadenectomy. A total of 82 patients were treated with c-RT, whereas the remaining 79 patients underwent IMRT. Intracavitary brachytherapy and concurrent chemotherapy were performed during external irradiation.ResultsThe mean dose delivered to the planning target volume was significantly higher in the IMRT group than in the c-RT group (61.8 vs 50.3 Gy,P= 0.029). Intensity-modulated radiation therapy plans yielded better dose sparing of small bowel, bladder, and rectum than did c-RT (P< 0.05). Moreover, the IMRT patients experienced less acute and chronic toxicities (P< 0.05) and better short-term effects (complete response + partial response) than did those treated with c-RT (89.9% vs 63.4%,P= 0.03). Three- and 5-year overall survival rates were significantly higher in the IMRT group than in the c-RT group (3-year: 58.4% vs 39.1%,P= 0.012; 5-year: 35.4% vs 21.4%,P= 0.007). Furthermore, 5-year progression-free survival rates were significantly higher in the IMRT group than in the c-RT group (26.1% vs 15.1%,P= 0.031).ConclusionsIntensity-modulated radiation therapy achieved outcomes superior to c-RT in patients with pelvic locoregional recurrence of cervical cancer after radical surgery. The acute and chronic toxicities were acceptable, and the adjacent organs at risk were well protected.

To analyze the CT characteristics and pathological classification of early lung adenocarcinoma (T1N0M0) with pure ground-glass opacity (pGGO). Ninety-four lesions with pGGO on CT in 88 patients with T1N0M0 lung adenocarcinoma were selected from January 2010 to December 2012. All lesions were confirmed by pathology. CT appearances were analyzed including lesion location, size, density, uniformity, shape, margin, tumour-lung interface, internal and surrounding malignant signs. Lesion size and density were compared using analysis of variance, lesion size also assessed using ROC curves. Gender of patients, lesion location and CT appearances were compared using χ2-test. There were no significant differences in gender, lesion location and density with histological invasiveness (P > 0.05). The ROC curve showed that the possibility of invasive lesion was 88.73 % when diameter of lesion was more than 10.5 mm. There was a significant difference between lesion uniformity and histological invasiveness (P = 0.01). There were significant differences in margin, tumour-lung interface, air bronchogram with histological invasiveness ( P = 0.02,P = 0.00,P = 0.048). The correlation index of lesion size and uniformity was r = 0.45 (P = 0.00). The lesion size and uniformity, tumour-lung interface and the air bronchogram can help predict invasive extent of early stage lung adenocarcinoma with pGGO. • CT characteristics and pathological classification of pGGO lung adenocarcinoma smaller than 3 cm • The optimal cut-off value for discriminating preinvasive from invasive lesions was 10.5 mm • Uniformity was significant difference between histological subtypes and correlated with lesion size • Tumour margin, tumour-lung interface and air bronchogram showed different between histological types • No significant difference in gender, lesion location and density with histological subtypes

Summary Objectives MicroRNA (miRNA) machinery regulates cancer cell behavior, and has been implicated in patients’ clinical status and prognosis. We found that microRNA-29b (miR-29b) increased significantly in advanced migratory cells. However, miR-29b controls the migration ability, and its regulatory mechanism in oral squamous cell carcinoma (OSCC) remains unknown. Materials and methods We triggered miR-29b expression in OSCC patients and cell lines by conducting real-time quantitative PCR. We determined the functions of miR-29b in the migration of OSCC cells by using gain- and loss-of-function approaches. We elevated the target genes of miR29b through software predictions and a luciferase report assay. We used an orthotopic OSCC animal model to investigate the effects of miR29b on OSCC cell metastasis in vivo. Results The clinical data revealed that miR-29b expression was correlated with lymph node metastasis and an advanced tumor stage in 98 OSCC patients. Furthermore, multivariate analysis revealed that miR-29b expression was significantly correlated with recurrence, and indicated poor survival. MiR-29b promoted OSCC cell migration and downregulated CX3CL1, a cell–cell adhesion regulator, which plays an essential role in miR-29b-regulated OSCC cell migration machinery. Furthermore, we found that CX3CL1 expression was correlated with lymph node metastasis and an early tumor stage in OSCC patients, and negatively correlated with miR-29b expression. Conclusion MiR-29b acts as an oncomir, promoting cell migration through CX3CL1 suppression, and could be a potential therapeutic target for preventing OSCC progression.

Objective To identify the optimal ratio of free femur for minimizing the risks of periprosthetic fracture. Methods Three dimensional models of the femur with hip and knee stem elongation were constructed. With the distal femoral condylar surface fixed in a three dimensional model, the femoral head loading was performed according to the methods described by Huiskes and van Rietbergen in the models of hip replacement, knee replacement with or without hip stem or knee stem elongation. The maximum principal stress (MPS) and maximum principal elastic strain (MPES) of the femur were recorded and their relationships to the free femur ratio were analyzed using Pearson's correlation analysis. Results There were no obvious changes in MPS and MPES with hip stem elongation from 100 to 180 mm. In ipsilateral hip and knee replacement, the MPS and MPES had a tendency to decrease with knee and hip stem elongation. The MPS and MPES were mainly located in the anterior medial side of the middle to distal femur post-hip replacement and distalized with stem elongation. When the knee stem had been elongated more than 120 mm, the stress and strain concentrated strongly in the middle of the femoral shaft. There was a positive correlation between MPS and MPES to the free femur ratio (P < 0.01); however, no optimal ratio of free femur that would minimize the risks of periprosthetic fracture was identified. Conclusion Positive correlations were found between implant free femur and stress and strain changes in total knee arthroplasty, total hip arthroplasty and ipsilateral hip and knee replacement.

CCN family members are involved in many physiologic and pathological functions, and be detected in many different cancer types. Immunohistochemistry (IHC) is an important diagnostic pathology tool to demonstrate protein expression in clinical and research fields. Here, we explain the preparation of sample slides, staining procedure, and the problems that might be met during the time. The differential staining of CCN proteins is shown in breast cancer, oral cancer, lung cancer, colorectal cancer, and gastric cancer.

To investigate the feasibility of low-tube-voltage (80 kVp) coronary CT angiography (CCTA) combined with contrast medium (CM) reduction and iterative model reconstruction (IMR) on patients with standard body mass index compared with clinical routine protocol.Retrospectively gated helical CCTA scans were acquired using a 256-slice multi-slice CT (Brilliance iCT; Philips Healthcare, Cleveland, OH) on 94 patients with standard body mass index (20-25 kg m(-2)) who were randomly assigned into 2 groups. The scan protocol for Group 1 was 100 kVp and 600 mAs with 70 ml CM at an injection rate of 4.5-5.5 ml s(-1); images were reconstructed by a hybrid iterative reconstruction technique (iDose(4); Philips Healthcare). Group 2 was scanned at 80 kVp and 600 mAs with 35 ml CM at an injection rate of 3.5-4.5 ml s(-1); images were reconstructed with IMR. Objective measurements such as the mean image noise and contrast-to-noise ratio of the two groups were measured on CT images and compared using the paired t-test. In addition, a subjective image quality evaluation was performed by two radiologists who were blinded to the scan protocol, using a 5-point scale [1 (poor) to 5 (excellent)]. The results of the two groups were compared using Mann-Whitney U test.The iodine delivery rate of Group 2 was 1.0 ± 0.5 gI s(-1) compared with 2.1 ± 0.5 gI s(-1) in Group 1 resulting in a reduction of 52.4%. In addition, an effective radiation dose reduction of 56.4% was achieved in Group 2 (2.4 ± 1.2 mSv) compared with Group 1 (5.5 ± 1.4 mSv). The mean CT attenuation, contrast-to-noise ratio and image quality of all segments in Group 2 were significantly improved compared with those in Group 1 (all, p 0.01).The use of IMR along with a low tube voltage (80 kVp) combined with a low CM protocol for CCTA can reduce both radiation and CM dose with improved image quality.In this study, we used a novel knowledge-based IMR which remarkably reduced the image noise. We compared the quality of the images obtained when the tube voltage was reduced to 80 kVp and that of those obtained according to the clinical routine protocols to determine whether ultra-low-dose imaging plus IMR is feasible in CCTA scans. We found that a low dose protocol combined with 80 kVp and reduced CM for CCTA can reduce both radiation dose and CM dose with improved image quality by the use of IMR in non-obese patients.

Brain-derived neurotrophic factor (BDNF) plays an important role in learning and memory in multiple brain areas. In the present study, we investigated the roles of BDNF in aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats.Conditioned place aversion (CPA) was induced in male SD rats exposed to a single dose of morphine (10 mg/kg, sc) followed by naloxone (0.3 mg/kg, sc). In some rats, BDNF receptor antagonist K252a (8.5 ng per side) or BDNF scavenger TrkB-FC (0.65 μg per side) was bilaterally microinjected into amygdala before naloxone injection. BDNF mRNA and protein expression levels in amygdala were detected after the behavior testing.CPA behavior was induced in rats by the naloxone-precipitated morphine withdrawal, which was accompanied by significantly increased levels of BDNF mRNA and protein in the amygdala. Bilateral microinjection of TrkB-FC or K252a into the amygdala completely blocked CPA behavior in the rats.Formation of aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats requires BDNF expression in the amygdala.

Background Anterior cervical decompression and fusion (ACDF) has long been the preferred treatment for cervical spondylotic myelopathy (CSM). However, few studies have focused on surgical results of CSM in patients with developmental canal stenosis (DCS). The purpose of this study was to investigate DCS as a comorbidity in patients with CSM and the correlation between surgical results and DCS. Methods From January 1995 to December 2005, 122 patients treated with ACDF for CSM were enrolled in this retrospective study. Pavlov’s ratio was used to evaluate cervical spinal canal size, with a value of

Background To study the distribution pattern of lymph node metastases of stage IA to IIA cervical cancer and to clarify the individualized clinical target volume delineation of regional lymph nodes (CTVn). Methods A total of 665 cases with International Federation Gynecology and Obstetrics stage IA to IIA cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. The clinicopathological factors related to lymph node metastases were analyzed using logistic regression analysis. Results Pelvic lymph node metastases were found in 168 of 665 patients resulting in a metastasis rate of 25.3%. Binary logistic regression analysis showed that age, lymph vascular space involvement, and deep stromal invasion statistically influenced pelvic lymph node metastases (p = 0.017

ObjectivesThis study aimed to investigate the metastatic rate of circumflex iliac node distal to the external iliac node (CINDEIN) and its associations with clinicopathological factors in patients with stage IA to IIA cervical cancer to determine whether dissection of CINDEIN had a role in surgery of these patients.MethodsSix hundred thirty-three patients with the International Federation of Gynecology and Obstetrics stage IA to IIA cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. The metastatic rate and distribution of the pelvic lymph nodes (PLNs) and CINDEINs were analyzed.ResultsThe PLN metastatic rate was 25.6% (162 of 633 patients). Sixteen of 162 node-positive patients had CINDEIN metastases. Only 1 patient without PLN metastases had positive CINDEIN nodes. Univariate analysis revealed that other PLNs (including lymph nodes collected from obturator, external iliac, and internal iliac regions) and lymph vascular space involvement were the risk factors of CINDEIN metastases (P < 0.05). Other PLN metastasis (odds ratio, 50.6; 95% confidence interval, 6.6–386.7) was an independent risk factor for metastasis to CINDEIN by binary logistic regression analysis.ConclusionsCircumflex iliac node distal to the external iliac node metastases seemed to occur secondarily to widespread PLN metastases. In early stage cervical cancer, removal of the CINDEIN as a routine surgical procedure might be omitted to reduce operation time and minimize surgical morbidity.

Full article available online at ORTHOSuperSite.com. Search: 20120123-09 Surgical decision making for femoral neck fractures is currently based on factors such as patient age, fracture type, and medical condition, lacking a quantitative standard. The treatment protocol based on such qualitative assessment has poor operability, greatly affected by the surgeon’s subjective factors. As a result, a quantitative score system (QSS) focusing on 5 factors—age, fracture type, bone mineral density, activities of daily living, and medical comorbidities—with a total score of 25 is designed to deal with adult femoral neck fractures. The higher the score, the worse the patient’s physiological condition. According to our clinical experience, patients with 1 to 11 points should be treated with internal fi xation; patients with 12 to 17 points with total hip arthroplasty (THA), and patients with 18 to 22 points with hemiarthroplasty. Patients with 22 to 25 points should be treated with internal fi xation due to the high surgical risk of arthroplasty caused by poor physiological condition. Three hundred seventy-fi ve adult femoral neck fractures were treated on the basis of QSS for this 2-year prospective study. Of these, 242 were treated with low-score internal fi xation, 60 with THA, 55 with hemiarthroplasty, and 18 with high-score internal fi xation. The revision rates 2 years postoperatively in the low-score internal fi xation, THA, and hemiarthroplasty groups were 15.3%, 5.0%, and 5.5%, respectively, which were lower than those from a meta-analysis (internal fi xation, 35%; THA, 16%). This QSS helps surgical decision making regarding the treatment choice for adult patients with femoral neck fractures, and good results in preliminary clinical practice have been achieved.

Considerable evidence suggests that monocytes/macrophages play a crucial role in the process of liver injury and repair. Recent investigations have focused on the function of various macrophage-produced cytokines in liver disease. Much is still unknown, however, about the mechanism of macrophage recruitment and activation during liver disease. To further define this process, the gene expression of the monocyte chemoattractant monocyte chemoattractant protein 1 (MCP-1) was examined in animal and human liver disease. MCP-1 mRNA was not found in normal rat liver by Northern blot analysis. After single-dose treatments with the hepatotoxins carbon tetrachloride and galactosamine, MCP-1 mRNA was detectable beginning at 2 and 4 h after treatment, respectively, and was expressed continuously until 60–72 h. During chronic carbon tetrachloride administration, MCP-1 mRNA levels were elevated for the entire 10 weeks of treatment with peak levels of expression occurring early (weeks 1–3) and late (weeks 8–10) in this model. Isolated liver cell fractions from rats treated for 3 weeks with carbon tetrachloride revealed the major cellular source of MCP-1 mRNA to be fat-storing or Ito cells, with some expression occurring in the endothelial cell fraction. Studies of potential inducers of hepatic MCP-1 expression showed that lipopolysaccharide, tumor necrosis factor-α, and interleukin-lα and β treatments all led to MCP-1 expression. Finally, studies of human liver samples revealed MCP-1 gene expression in nondiseased liver and greatly increased levels in livers from patients with fulminant hepatic failure. These data implicate MCP-1 from fat-storing cells as a modulator of the process of liver injury and further support a role for MCP-1 in the pathogenesis of human disease. J. Leukoc. Biol. 55: 120–126; 1994.

To evaluate the features of stent gap (SG) and the long-term impact of SG on in-stent restenosis (ISR) in patent stents.A total of 347 consecutive patients with 781 stents who underwent MDCT were assessed for SG and ISR. Clinical and stent features were compared between the SG and non-SG groups. In the follow-up study, among 82 patients with 175 patent stents [26 assessed by conventional coronary angiography (CCA) including 6 contacted in a telephone survey, 46 assessed by computed tomography angiography (CTA) and 10 by both], the incidence of ISR was compared between stents with and without SG.Three patients and 13 stents were excluded. SG was observed in 12.5% of patients and 8.6% of stents. ISR detected by CTA was noted in 21.2% of SG, and SG accounted for 23.7% of ISR. Stent number, length, location, overlapping pattern, tortuosity and in-out angle were predisposing factors for SG. During a mean follow-up period of 15 months after detection of SG, the incidence of ISR was significantly higher in the SG group than in the non-SG group (43.8/14.9% by CCA, 33.3/10.1% by CTA and CCA).Patent stents with SG detected by CTA had a higher incidence of late restenosis, indicating that long-term follow-up or further intervention is necessary.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been implicated in tumor development and progression. The aim of this study was to investigate the role of TWEAK in colorectal cancer (CRC) progression.To investigate the involvement of TWEAK in the progression of human CRC, normal, and tumor specimens from 174 patients were analyzed immunohistochemically for the expression of TWEAK. TWEAK recombinant protein treatment, transfection of expression plasmids, and small interfering RNA to knockdown TWEAK expression were performed to test invasive ability with a Boyden chamber. The mRNA expression profile in recombinant TWEAK treatment was compared to a control group by microarray analysis. To identify downstream effectors, Raf kinase inhibitor (RKIP) and its correlation with TWEAK in vitro and in vivo were examined by quantitative real-time polymerase chain reaction and invasion assays.CRC patients whose tumors displayed high TWEAK expression had a statistically significantly higher overall survival and a disease-free advantage over those with a low TWEAK expression. In in vitro invasion assays, alterations in TWEAK expression in CRC cell lines inversely modulated their invasive ability. By means of integrated genomics, we identified RKIP as a downstream effector in TWEAK-mediated invasion inhibition. Knockout of RKIP expression in HCT116 cells by short hairpin RNA (shRKIP) resulted in increased invasiveness. Clinically, RKIP and TWEAK mRNA expression showed strong positive correlations in CRC patient samples.Our results implicate TWEAK as a key regulator of CRC invasion, and it appears to be a useful prognostic factor for patients with CRC.

In previous studies, glycolysis machinery has been identified as a regulating pathway in cancer cell. However, the role of glycolysis in oral squamous cell carcinoma (OSCC) progression is still largely unknown. Fructose-bisphosphate aldolase C (ALDOC), one of the key enzymes in glycolysis, expresses in OSCC patients and cell lines and detects by real-time quantitative RT-PCR. The functions of ALDOC were determined by gain and loss function approaches and the orthotopic animal model was performed. ALDOC mRNA and protein expression was significantly decreased in advanced migratory cell and negatively correlated with lymph node metastasis and advanced tumor TNM stage in OSCC patients. In conclusion, ALDOC plays as an OSCC prognosis marker clinically, and functions to suppress OSCC cell migration and invasion. ALDOC could be a potential therapeutic target to block OSCC progression. Citation Format: Yueju Li, Tse-Hung Huang, Been-Ren Lin, Cheng-Chi Chang. The regulatory effect of fructose-bisphosphate aldolase C in oral squamous cell carcinoma progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1152. doi:10.1158/1538-7445.AM2015-1152

The age-related decline of learning and memory is a common phenomenon in humans and animals, even though the underlying mechanism is not yet known. In the present study, we propose that synaptotagmin 1 (Syt 1) might be a synaptic protein involved in the loss of learning and memory with aging. To test this hypothesis, the age-related spatial cognitive ability of 36 P8 mice (15 mice aged 4 months, 11 mice aged 8 months and 10 mice aged 13 months) was measured in a Morris water maze. After the behavioral test, both the protein and mRNA levels of Syt 1 were determined in the dorsal hippocampus by means of immunocytochemistry and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. In the Morris water maze, the latency of the 4-month mice to find the submerged platform was significantly shorter than that of the older mice, while there were no significant differences between the 8- and 13-month-old mice in this respect. Compared to the 4-month-old mice, the Syt 1 protein in the 13-month-old mice was significantly increased in almost all layers of each subfield of the hippocampus. The average level of Syt 1 mRNA in the dorsal hippocampus of the P8 mice had not changed with aging. The latency of the 13-month-old P8 mice tested in the Morris water maze was positively correlated with the Syt 1 immunoreactivity in four circuit-specific regions in the dorsal hippocampus. Interestingly, the latency in the Morris water maze was also positively correlated with the level of Syt 1 mRNA in the dorsal hippocampus in individual aged P8 mouse. These results suggest that increased Syt 1 in the dorsal hippocampus in aged mice might be responsible for the age-related impairment of learning and memory.

Alzheimer's disease (AD) is characterized pathologically by selective neuronal loss and by the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs). Since calcium/calmodulin-dependent protein kinase II-alpha (CaMKII-alpha), one of the most abundant kinases in the brain, is involved in the phosphorylation of tau and amyloid precursor protein (APP), we examined the expression of CaMKII-alpha and its relationships with the neuropathology in the hippocampus of AD patients using immunohistochemistry and double-labeling immunofluorescence methods. The results showed that CaMKII-alpha containing neurons were selectively lost in the CA1 subfield of AD hippocampus and accompanied with enhanced immunoreactivity in the remaining neurons. About 33% hyperphosphorylated tau-containing neurons labeled by monoclonal antibody AT-8 were also immunoreactive for CaMKII-alpha. Moreover, we found for the first time that the immunoreactivity of CaMKII-alpha was largely deposited in the SPs of the AD hippocampus. The pattern of the co-localization of CaMKII-alpha with beta amyloid depended on the type of SPs. Since the co-localization of CaMKII-alpha with hyperphosphorylated tau is relatively rare, we concluded that CaMKII-alpha may be related with beta-amyloid more closely than being involved in tau hyperphosphorylation.

A battery of tasks, i.e. beam walking, open field, tightrope, radial six-arm water maze (RAWM), novel-object recognition and olfactory discrimination, was used to determine whether there was age- and sex-related memory deterioration in Kunming (KM) mice, and whether these tasks are independent or correlated with each other. Two age groups of KM mice were used: a younger group (7-8 months old, 12 males and 11 females) and an older group (17-18 months old, 12 males and 12 females). The results showed that the spatial learning ability and memory in the RAWM were lower in older female KM mice relative to younger female mice and older male mice. Consistent with this, in the novel-object recognition task, a non-spatial cognitive task, older female mice but not older male mice had impairment of short-term memory. In olfactory discrimination, another non-spatial task, the older mice retained this ability. Interestingly, female mice performed better than males, especially in the younger group. The older females exhibited sensorimotor impairment in the tightrope task and low locomotor activity in the open-field task. Moreover, older mice spent a longer time in the peripheral squares of the open-field than younger ones. The non-spatial cognitive performance in the novel-object recognition and olfactory discrimination tasks was related to performance in the open-field, whereas the spatial cognitive performance in the RAWM was not related to performance in any of the three sensorimotor tasks. These results suggest that disturbance of spatial learning and memory, as well as selective impairment of non-spatial learning and memory, existed in older female KM mice.